Abnormal miR-148b Expression Promotes Aberrant Glycosylation of IgA1 in IgA Nephropathy
- 1 May 2012
- journal article
- Published by Ovid Technologies (Wolters Kluwer Health) in Journal of the American Society of Nephrology
- Vol. 23 (5), 814-824
- https://doi.org/10.1681/asn.2011060567
Abstract
Aberrant O-glycosylation in the hinge region of IgA1 characterizes IgA nephropathy. The mechanisms underlying this abnormal glycosylation are not well understood, but reduced expression of the enzyme core 1, β1,3-galactosyltransferase 1 (C1GALT1) may contribute. In this study, high-throughput microRNA (miRNA) profiling identified 37 miRNAs differentially expressed in PBMCs of patients with IgA nephropathy compared with healthy persons. Among them, we observed upregulation of miR-148b, which potentially targets C1GALT1. Patients with IgA nephropathy exhibited lower C1GALT1 expression, which negatively correlated with miR-148b expression. Transfection of PBMCs from healthy persons with a miR-148b mimic reduced endogenous C1GALT1 mRNA levels threefold. Conversely, loss of miR-148b function in PBMCs of patients with IgA nephropathy increased C1GALT1 mRNA and protein levels to those observed in healthy persons. Moreover, we found that upregulation of miR-148b directly correlated with levels of galactose-deficient IgA1. In vitro, we used an IgA1-producing cell line to confirm that miR-148b modulates IgA1 O-glycosylation and the levels of secreted galactose-deficient IgA1. Taken together, these data suggest a role for miRNAs in the pathogenesis of IgA nephropathy. Abnormal expression of miR-148b may explain the aberrant glycosylation of IgA1, providing a potential pharmacologic target for IgA nephropathy.Keywords
This publication has 49 references indexed in Scilit:
- MicroSNiPer: a web tool for prediction of SNP effects on putative microRNA targetsHuman Mutation, 2010
- Identification of a microRNA signature of renal ischemia reperfusion injuryProceedings of the National Academy of Sciences of the United States of America, 2010
- Down-regulation of core 1 1,3-galactosyltransferase and Cosmc by Th2 cytokine alters O-glycosylation of IgA1Nephrology Dialysis Transplantation, 2010
- Identification of Unique MicroRNA Signature Associated with Lupus NephritisPLOS ONE, 2010
- MicroRNA expression profiles predictive of human renal allograft statusProceedings of the National Academy of Sciences of the United States of America, 2009
- Most mammalian mRNAs are conserved targets of microRNAsGenome Research, 2008
- IgA1-secreting cell lines from patients with IgA nephropathy produce aberrantly glycosylated IgA1JCI Insight, 2008
- Reactivities of N-acetylgalactosamine-specific lectins with human IgA1 proteinsMolecular Immunology, 2007
- Combinatorial microRNA target predictionsNature Genetics, 2005
- Statistical significance for genomewide studiesProceedings of the National Academy of Sciences of the United States of America, 2003